Through multidisciplinary interactions and collaborations involving immunologists, organic chemists, nanostructural chemists and neuroscientists, we will employ a bottom-up strategy to engineer nicotine hapten, T helper cell peptides and adjuvant onto self-assembling DNA nanoscaffolds in a controllable fashion to induce T-cell dependent anti-nicotine antibody responses. Robust and versatile synthesis and assembly of various antigenic components onto DNA-nanoscaffolds along with step-wise screening afford opportunities to identify optimal combinations and configurations of the nanovaccine for the induction of strong, anti-nicotine antibody responses, leading to production of high titer and high affinity anti-nicotine antibodies for treatment of nicotine dependence. It is conceivable that this approach can be readily extended to the development of any vaccines, including those targeting drugs of abuse, microbial pathogens and tumor antigens. Thus, the project represents a proof-of-concept investigation of a new and unconventional technology in vaccine construction. PUBLIC HEALTH RELEVANCE: We propose to develop novel DNA nanovaccines against nicotine. Through rational design and step-wise screenings, we aim to create effective nicotine vaccines to treat nicotine dependence toward a longer-term goal of reducing tobacco-related diseases.